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Biomedical subjects

O Faergeman

Publications and source records attributed to O Faergeman.

At least 109 records · Page 6Linked to original sources

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).

Female↗

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension.

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril, 50 to 100 mg metoprolol, 12.5 to 25 mg hydrochlorothiazide, and placebo, each given twice daily for 8 weeks. Antidiabetic treatment remained unchanged during the study. After receiving placebo for a 4 week run-in period, arterial blood pressure was 168/101 +/- 93/10 (mean +/- SEM) mm Hg. Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 +/- 2 mm Hg: captopril, 92 +/- 1 mm Hg; metoprolol, 90 +/- 1 mm Hg; hydrochlorothiazide, 91 +/- 1 mm Hg. Metabolic variables were not significantly altered by captopril and metoprolol, while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 +/- 0.3 to 8.2 +/- 0.4% (P less than .001), decreased high-density lipoprotein-cholesterol from 1.19 +/- 0.08 to 1.10 +/- 0.06 mmol/L (P less than .05). Glomerular filtration rate, urinary albumin excretion, orthostatic blood pressure response, and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods. The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo. We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function, while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile.

Aged↗

Normal lipoprotein(a) concentrations and apolipoprotein(a) isoforms in patients with insulin-dependent diabetes mellitus.

Lipoprotein(a) [Lp(a)] is an LDL particle in which apoliporotein B-100 is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated, and plasma Lp(a) concentrations above 20-30 mg dl-1 are an independant risk factor for ischaemic heart disease (IHD). To investigate whether Lp(a) could be important for the high cardiovascular mortality rate in patients with insulin dependent diabetes mellitus (IDDM), we determined Lp(a) concentrations and phenotypes in a group of 108 men (median age 32 years) with IDDM without nephropathy. A group of 40-year-old men (n = 466) served as controls. The median Lp(a) concentration was 7.4 mg dl-1 [95% CI 4.9 to 11.7] in the diabetic patients and 6.3 mg dl-1 [95% CI 5.2 to 7.0] in controls. The Lp(a) concentration exceeded 30 mg dl-1 in 22% of IDDM patients and in 20% of controls (P = 0.13). Moreover, the distribution of apo(a) phenotypes did not differ between patients and control. Lp(a) levels and apo(a) phenotypes are thus apparently the same in IDDM patients without nephropathy and controls. These findings do not exclude the possibility that Lp(a) may be increased in patients with nephropathy in whom coronary artery disease frequently co-exist or that Lp(a) in a given concentration is more atherogenic in IDDM patients than in persons without IDDM.

Apolipoproteins↗

Significant association between low-molecular-weight apolipoprotein(a) isoforms and intermittent claudication.

The role of lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) isoforms in symptomatic peripheral atherosclerosis was studied in 100 randomly selected middle-aged (45-69 years) men with intermittent claudication (IC) and 100 randomly selected healthy control (C) subjects. IC and C subjects were matched pairwise for sex, age, and smoking habits. Plasma Lp(a) concentrations were significantly higher in IC subjects, with a median value of 20.12 mg/dl, compared with 11.11 mg/dl in C subjects (p less than 0.0009). The elevated Lp(a) concentration was to a great extent due to a significant difference in the frequency distribution of apo(a) isoforms between IC and C subjects (p less than 0.029). Low-molecular-weight apo(a) isoforms were more prevalent in IC than C subjects. Also, IC subjects with apo(a) S2 and S3 phenotypes had higher Lp(a) concentrations than control subjects with the same phenotypes: S2:60.70 mg/dl (IC) and 48.69 mg/dl (C), p less than 0.038; and S3: 30.18 mg/dl (IC) and 12.01 mg/dl (C), p less than 0.042, so other still-unknown factors, genetic or nongenetic, may be important. Stepwise logistic regression analysis demonstrated that Lp(a) concentration contributed significantly (p less than 0.0002) to IC, independent of age, smoking, hypertension, diabetes mellitus, plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apo B, and plasma total triglycerides. Apo(a) isoforms grouped according to molecular weight were also independent of the above risk factors associated (p = 0.016) with the occurrence of IC because of their low-molecular-weight but were not independent of Lp(a) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[The role of oat bran in the treatment of hypercholesterolemia].

Review of published studies suggests that high dietary content of soluble fibre can reduce serum cholesterol by up to 17%. The reduction may be proportional to the degree of hypercholesterolemia before the change in diet. The mechanism is not fully elucidated. It may be analogous to the effect of anion-binding-resins on the metabolism of bile acids and cholesterol but it may also be due to partial substitution of soluble fibre for dietary saturated fat which causes elevation in serum cholesterol.

Dietary Fiber↗

[Non-dietary, non-pharmacological treatment of severe hypercholesterolemia].

Non-dietary, non-pharmacological reduction of cholesterol in patients with severe hypercholesterolemia can be obtained by partial ileal by-pass, portacaval shunt operation or liver transplantation. A non-surgical method is apheresis, by which low density and very low density lipoproteins are removed from blood in an extracorporal circulation system. Apheresis methods include plasmapheresis, immunoadsorption, chemical affinity and Double Membrane Filtration. Treatment of a 30 year old man with severe familial hypercholesterolemia and ischaemic heart disease, by LDL-apheresis, resulted in an average decline in serum-cholesterol of 35%. LDL-apheresis is indicated in the treatment of this type of patient and in homozygous familial hypercholesterolemia.

Adult↗

Repetitive sequences involved in the recombination leading to deletion of exon 5 of the low-density-lipoprotein receptor gene in a patient with familial hypercholesterolemia.

Alu sequences in the low-density-lipoprotein (LDL) receptor gene are suspected of being of importance for the creation of gene defects leading to familial hypercholesterolemia (FH). One potential mechanism is that Alu sequences undergo homologous recombination, producing deletions or duplications of DNA segments on genomic DNA. In at least four cases (FH626, PO, JA and FH-DK3), a deletion of exon 5 of the LDL receptor gene has been reported. Only one of these (FH626) have so far been characterized in detail by sequence analysis and shown to involve two of the Alu repeated sequences, which are present in introns 4 and 5. We here report the complete characterization of FH-DK3 and show that the cross-over break points involve sequences similar, but not at identical positions in the 5' end, to those reported for FH626. The recombinations in both FH-DK3 and FH626 are suggested to have occurred within a 22-bp repeated sequence found in both junction alleles.

Base Sequence↗

Comparison of the effects of xamoterol, atenolol and propranolol on breathlessness, fatigue and plasma electrolytes during exercise in healthy volunteers.

The influence of clinical doses of drugs that affect beta-adrenoceptors has been examined on heart rate, blood pressure, duration of exercise, and on electrolyte concentrations (Na, K, Ca and Mg) during recovery from exercise in healthy volunteers. The drugs used were a beta 1-adrenoceptor antagonist atenolol, a nonselective beta-adrenoceptor antagonist propranolol, and a cardioselective, partial beta 1-adrenoceptor agonist with 43% ISA activity, xamoterol. The duration of exercise was smaller on propranolol. Maximum exercise heart rate and blood pressure were reduced significantly by propranolol and atenolol. Xamoterol reduced maximum exercise heart rate and had no effect on blood pressure. The degree of breathlessness and fatigue revealed no differences between treatments. Recent evidence has suggested an association between hyperkalaemia and hypomagnesaemia with an increase in the occurrence of arrythmias following acute myocardial infarction. Exercise-induced hyperkalaemia has been suggested as a factor in sudden death. The results confirmed a rise in serum potassium during exercise and attenuation of the fall during recovery under beta-adrenoceptor blockade. Xamoterol was no different from placebo in these respects. Exercise also produced a rise in magnesium levels and during recovery the level fell below baseline. Both these effects were attenuated by propranolol. Calcium levels were not affected by any of the treatments.

Adrenergic beta-Agonists↗

The psychosocial work environment of younger men surviving acute myocardial infarction.

In a retrospective, consecutive case-control study, the psychosocial work environment of 52 men younger than 55 years, who had survived an acute myocardial infarction, was analysed with respect to workload and work quality using a comprehensive self-administered questionnaire. Patients more frequently reported exhaustion after work, had less responsibility at their job, held less well esteemed positions, and had less possibility of social contact during working hours. These differences bore no simple relationship to social class or conventional risk factor distribution, although higher workloads were associated with a significantly higher frequency of smoking. The study suggests that the ideal cardioprotective job is a well esteemed job at a certain responsibility level with good conditions for social interaction during working hours, in which the experienced job demands are reasonable, and where extra resources are available if needed.

Adult↗

DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia.

DNA samples from 25 unrelated Danish patients with familial hypercholesterolemia (FH) were screened by Southern blot hybridization to detect gross alterations in the low density lipoprotein (LDL) receptor gene. Three FH-patients were found to have a deletion. Two of these delete part of the cysteine rich domain, which comprises the ligand binding region of the LDL-receptor. The third deletion encompasses coding regions for the cytoplasmic part of the receptor. As two of these deletions could be equivalent to previously described LDL-receptor gene alterations, these data seem to support a notion of recombination hot spots which involve Alu-sequences.

Adult↗

Detection of the apoB-3500 mutation (glutamine for arginine) by gene amplification and cleavage with MspI.

A single primer-template mismatch 2 bp from the apoB-3500 (G to A) mutation permits introduction of a cleavage site for MspI (C/CGG) in normal alleles but not in mutant alleles (CCAG). After amplification, cleavage, and polyacrylamide gel electrophoresis, normal and mutant alleles could be unambiguously distinguished. We constructed a positive (homozygous mutant) standard by site-directed mutagenesis. A negative standard was DNA from a homozygous normal subject. The method enables us to screen for the mutation with 12 microliters of spotted whole blood as the source of DNA.

Apolipoproteins B↗

[Measurement of cholesterol in capillary blood using the Reflotron system. Results from approximately 1,000 comparisons with reference measurements of cholesterol in venous serum].

The results of 969 measurements of total cholesterol in capillary blood from fingerstick, performed with the Reflotron-system in the field, were compared with measurements of total cholesterol in venous serum. The comparison allows an evaluation of the combined effect of differences in sample material, working place, stability of methods and staff training. The mean values for all measurement were nearly identical with the two methods, and approximately 95% of the Reflotron-measurements were within an interval of +/- 0.7 mmol/l around the estimated true value. However, values below approximately 6 mmol/l were systematically underestimated, and values above approximately 7 mmol/l were overestimated with the Reflotron-system. The coefficient of variation of the system is below 5%, but both this precision and the accuracy appear to be unstable. Evaluated as a tool in screening for hypercholesterolemia, measurements with the system resulted in a modest extent of erroneous classification of subjects, but the positive diagnostic predictive value of the statement "cholesterol above 7 mmol/l" is only approximately 76%. Simulations of likely variations in the accuracy and precision of the method show a significant influence on the extent of errors. It is recommended that measurements with the system are routinely controlled by measuring an appropriate control material, at the start of each run and after every 30 samples.

Adult↗

[A comparison of results of simple evaluation of the risk of ischemic heart disease with calculations based on a multiplicative model].

A simple model for detection of subjects at risk of ischaemic heart disease, based on the addition of scores for different risk factors (Anggaard EE, Land JM, Lenihan J et al. Br Med J 1986; 293: 177-80), is at present widely applied in Denmark. The model could be tested in a prospective study, or a historical follow-up study, but we do not have the possibilities to do so. Instead we have compared the risk score of the model with the estimated five-year coronary mortality risk (ECR) in 742 men aged 40-44 years, calculated on the basis of data from the Seven Countries Study. There is a reasonable consistency in this comparison, in spite of the different principles of calculation, the consideration of different risk factors and/or weighting of risk factors. For example, the model has a sensitivity of 71%, a specificity of 89% and a positive predictive value of 68% in detecting 40-44 year old men in the upper quartile of ECR. The "false positives" are often men, who for other reasons may require preventive medical attention (obese heavy smokers), and the "false negatives" are often men with isolated hypertension.

Adult↗

[Occurrence of cardiovascular risk factors among working Danish men 20-59 years of age].

The prevalence of risk factors for ischaemic heart disease (IHD) was recorded in 1,365 men aged 20-59 years in active employment. The purpose was to evaluate the implications of a high-risk strategy based on the rather conservative Danish guidelines for treatment of hypercholesterolemia. The prevalence of various risk factors depends on age, but in all, 1% had diabetes mellitus, 5% had a family history of premature IHD, 50% were smokers, 21% were obese, 12% had systolic blood pressure greater than or equal to 160 mmHg, 8% had diastolic blood pressure greater than or equal to 100 mmHg and 14% had serum cholesterol greater than 7 mmol/l. Only 24% had none of these risk factors and there was a considerable clustering of risk factors in certain subgroups. Approximately 34%, varying from 17% of the younger to 49% of the older, required medical follow-up as part of the high risk strategy. We have estimated the required number of visits to a general practitioner, if all Danish men aged 20-59 years were screened within three years and approximately 30% required follow-up for five years, with three visits in the first year and one thereafter. The number of visits peaks at 450 visits per year during the third year, and a number of circumstances could reduce this figure considerably. Multifactorial models to estimate risk in connection with screening should be adopted to the Danish guidelines for treatment of hypercholesterolemia and hypertension, and future guidelines for intervention should probably be integrated in such a multifactorial model. To practice preventive medicine, many physicians will need greater knowledge of dietary counselling.

Adult↗

[Recommendations for clinical-chemical departments: lipid-lipoprotein analysis].

The section for preventive cardiology within the Danish Society for Cardiology has established a lipid group with representatives from The Danish Society for Clinical Chemistry, The Danish Society for Internal Medicine, The Danish Society for Cardiology, The Danish Society of Hypertension, The Danish College of General Practitioners, and The Danish Paediatric Society. The lipid group has elaborated recommendations for clinical chemical departments regarding lipid and lipoprotein analyses. The group suggests that doctors ordering lipid and lipoprotein analyses are offered the following: S-Cholesterol (total), substance conc., (fPt)S-Triglycerides, substance conc., S-HDL-cholesterol, substance conc., and (fPt)S-LDL-cholesterol, substance conc. (calculated). It is recommended that the biological variation be minimized by sampling in a sitting position after a 15 minutes' rest and by basing the clinical decision on a minimum of 2-3 determinations with an interval of about one month. The analytical variations should be reduced to below 3% (calculated as the variation coefficient), and it is recommended that laboratories participate in external quality control systems at least four times annually by reporting at least two human reference materials with different concentrations. As the use of reference intervals dependent on age and sex, based on random samplings of the background population, are less informative, it is recommended to refer to cutoff values for the clinical decision. The following cutoff values are recommended: S-Cholesterol (total), substance conc.: 6 mmol/l, (fPt)S-Triglycerides, substance conc.; 2.5 mmol/l, S-HDL-cholesterol, substance conc.: 0.9 mmol/l (fPt)-LDL-cholesterol, substance conc. (calculated): 4.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Clinical↗